{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:09:09Z","timestamp":1791958149863,"version":"4.3.4"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["14230"],"award-info":[{"award-number":["14230"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gout is a painful arthritic inflammatory disease caused by buildup of monosodium urate (MSU) crystals in the joints. Colchicine, a microtubule-depolymerizing agent that is used in prophylaxis and treatment of acute gout flare, alleviates the painful inflammatory response to MSU crystals. Using i.p. and intra-articular mouse models of gout-like inflammation, we found that GEF-H1\/GEF-H1\/AHRGEF2, a microtubule-associated Rho-GEF, was necessary for the inhibitory effect of colchicine on neutrophil recruitment. GEF-H1 was required for neutrophil polarization in response to colchicine, characterized by uropod formation, accumulation of F-actin and myosin L chain at the leading edge, and accumulation of phosphorylated myosin L chain, flotillin-2, and P-selectin glycoprotein ligand-1 (PSGL-1) in the uropod. Wild-type neutrophils that were pre-exposed to colchicine failed to roll or accumulate on activated endothelial monolayers, whereas GEF-H1 knockout (GEF-H1\u2212\/\u2212) neutrophils were unaffected by treatment with colchicine. In vivo, colchicine blocked MSU-induced recruitment of neutrophils to the peritoneum and the synovium in wild-type mice, but not in GEF-H1\u2212\/\u2212 mice. Inhibition of macrophage IL-1\u03b2 production by colchicine was independent of GEF-H1, supporting a neutrophil-intrinsic mode of action. Our results suggest that the anti-inflammatory effects of colchicine in acute gout-like inflammation can be accounted for by inhibition of neutrophil-rolling interactions with the inflamed vasculature and occurs through GEF-H1\u2013dependent neutrophil stimulation by colchicine. These results contribute to our understanding of the therapeutic action of colchicine, and could inform the application of this drug in other conditions.<\/jats:p>","DOI":"10.4049\/jimmunol.1900783","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T21:55:20Z","timestamp":1605563720000},"page":"3300-3310","source":"Crossref","is-referenced-by-count":10,"title":["GEF-H1 Is Required for Colchicine Inhibition of Neutrophil Rolling and Recruitment in Mouse Models of Gout"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-094X","authenticated-orcid":false,"given":"Noah","family":"Fine","sequence":"first","affiliation":[{"name":"Faculty of Dentistry, University of Toronto , Toronto, Ontario M5G 1G6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Gracey","sequence":"additional","affiliation":[{"name":"Vlaams Institute for Biotechnology Centre for Inflammation Research , 9052 Ghent ,","place":["Belgium"]},{"name":"Department of Internal Medicine and Pediatrics, University of Ghent , 9000 Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Dimitriou","sequence":"additional","affiliation":[{"name":"Department of Immunology, Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario M5G 1L7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"La Rose","sequence":"additional","affiliation":[{"name":"Department of Immunology, Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario M5G 1L7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6248-5977","authenticated-orcid":false,"given":"Michael","family":"Glogauer","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto , Toronto, Ontario M5G 1G6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rottapel","sequence":"additional","affiliation":[{"name":"Department of Immunology, Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario M5G 1L7 ,","place":["Canada"]},{"name":"Department of Medicine, Ontario Institute for Cancer Research, University of Toronto , Toronto, Ontario M5G 1L7 ,","place":["Canada"]},{"name":"Division of Rheumatology, St. Michael\u2019s Hospital , Toronto, Ontario M5B 1W8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2025030417505985700_r1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar1906","article-title":"A concise history of gout and hyperuricemia and their treatment","volume":"8","author":"Nuki","year":"2006","journal-title":"Arthritis Res. 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